Quantitative estimation of retinal nerve fiber layer height in glaucoma and the relationship with optic nerve head topography and visual field

Purpose: The authors estimated the retinal nerve fiber layer height (RNFLH) measurements in patients with glaucoma compared with those in age-matched healthy subjects as obtained by the laser scanning tomography and assessed the relationship between RNFLH measurements and optic and visual field status. Methods: Parameters of optic nerve head topography and RNFLH were evaluated in 125 eyes of 21 healthy subjects and 104 patients with glaucoma using the Heidelberg Retina Tomograph ([HRT] Heidelberg Engineering GmbH, Heidelberg, Germany) for the entire disc area and for the superior 70°(50°temporal and 20°nasal to the vertical midline) and inferior 70°sectors of the optic disc. The mean deviation of the visual field, as determined by the Humphrey program 24-2 (Humphrey Instruments, Inc., San Leonardo, CA, U.S.A) was calculated in the entire field and in the superior and inferior Bjerrum area. Result: Retinal nerve fiber layer height parameters (mean RNFLH and RNFL cross-sectional area) were decreased significantly in patients with glaucoma compared with healthy individuals. Retinal nerve fiber layer height parameters was correlated strongly with rim volume, rim area, and cup/disc area ratio. Of the various topography measures, retinal nerve fiber layer (RNFL) parameters and cup/disc area ratio showed the strongest correlation with visual field mean deviation in patients with glaucoma. Conclusion: Retinal nerve fiber layer height measures were reduced substantially in patients with glaucoma compared with age-matched healthy subjects. Retinal nerve fiber layer height was correlated strongly with topographic optic disc parameters and visual field changes in patients with glaucoma.

Lower corneal hysteresis in glaucoma patients with acquired pit of the optic nerve (APON)

Objective: Acquired pit-like changes of the optic nerve head (APON) are characteristic of glaucomatous damage and may be a sign of a localized susceptibility of the optic nerve. Thus, it is possible that biomechanical properties of the ocular tissues may play a pressure-independent role in the pathogenesis of glaucoma. Corneal hysteresis (CH) appears to provide information of the biomechanical properties of the ocular hull tissues. The purpose of this study was to compare CH of patients with primary open angle glaucoma (POAG) with and without APON. Methods: A prospective case control study was done. POAG patients with and without APON were measured using the Ocular Response Analyzer by masked investigators. Patients in both groups were matched for sex, age, corneal thickness, and type of glaucoma according to maximal IOP (NTG or POAG). Statistical analysis was done using ANOVA. Results: Corneal hysteresis of 16 glaucomatous eyes with APON and 32 controls (glaucoma without APON) was measured. The mean (±SD) CH in the APON group was 8.89 (±1.53) and 10.2 (±1.05) in the control group. The difference is statistically significant (p = 0.005). Conclusions: Corneal hysteresis in POAG patients with APON was significantly lower than in patients that did not have such structural changes of the optic disc. These findings may reflect pressure-independent mechanisms involved in the pathogenesis of such glaucomatous optic nerve changes. © Springer-Verlag 2007.

Effects of short term increase of intraocular pressure on optic disc cupping

Aims. To evaluate the effect of acute elevation of intraocular pressure (IOP) on optic disc cupping. Methods. 10 emmetropic and 10 myopic volunteers were included in this study. The cup area (CA) and cup volume (CV) of the optic disc were determined with the Heidelberg retina tomograph (HRT). After baseline determinations, a suction cup was used to increase the intraocular pressure (IOP) to 20-25 mmHg above the baseline and HRT images were obtained. Results. Baseline IOP was 13.5 (SD 1.3) mmHg and 12.6 (2.6) mmHg in the emmetropic and myopic groups, respectively. The IOP was elevated to 35.4 (3.3) mmHg and 34.4 (2.5) mmHg in the emmetropic and myopic groups, respectively. When compared with their baseline values, the cupping variables (CA and CV) were significantly increased (p <0.05) during the suction treatment in both emmetropic and myopic subjects. Conclusion. There was a significant enlargement in the optic disc cupping during the artificial increment of intraocular pressure in both emmetropic and myopic eyes. In non-glaucomatous eyes the optic nerve head has a partially dynamic topography dependent upon the level of IOP.

Reversal of optic disc cupping after glaucoma surgery analyzed with a scanning laser tomograph

Objective: To detect and quantitate changes in optic nerve morphology after glaucoma surgery using the Heidelberg Retina Tomograph (HRT, Heidelberg Instruments, Heidelberg, Germany). Design: Nonconsecutive observational case series. Participants and Intervention: The authors prospectively enrolled 21 adult patients undergoing incisional glaucoma surgery for progressive glaucoma damage. Quantitative analysis of the optic nerve head by scanning laser tomography and automated perimetry were performed before and after glaucoma surgery. Main Outcome Measures: Changes in optic nerve parameters were subjected to linear regression analysis with respect to percent of postoperative reduction of intraocular pressure (IOP), as well as with respect to age, refraction, preoperative cup:disc ratio, and change in visual field parameters. Results: Seventeen patients had pre- and postoperative images suitable for analysis. Mean IOP at the time of image acquisition before surgery was 30.5 ± 12 mmHg, and after surgery 11.8 ± 5.2 mmHg (mean follow-up, 26 ± 7 weeks). Eleven of 13 (85%) patients having IOP reduction of greater than 40% showed improvement in optic disc parameters. All four patients with less than 25% reduction in IOP showed worsening of most parameters. Changes in optic disc parameters were highly correlated with percent IOP reduction and with age. The parameters in which change most strongly correlated with percent change of IOP were cup area, rim area, cup:disc ratio, and mean cup depth (each, P <0.005). The age of the patient correlated highly with change in maximum cup depth (P <0.005). Refraction and clinically determined cup:disc ratio correlated poorly with changes in measured optic disc parameters. Clinical improvement in visual fields was correlated with the degree of improvement of cup:disc ratio (P = 0.025). Conclusion: Most patients showing a 40% lowering of IOP after glaucoma surgery show improved optic nerve morphology as measured by the HRT. The amount of improvement correlated highly with the percent reduction of IOP.

Potential role of intensity-modulated radiotherapy in the treatment of tumors of the maxillary sinus.

To assess 3-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) techniques to see whether doses to critical structures could be reduced while maintaining planning target volume (PTV) coverage in patients receiving conventional radiotherapy (RT) for carcinoma of the maxillary sinus because of the risk of radiation-induced complications, particularly visual loss. Six patients who had recently received conventional RT for carcinoma of the maxillary sinus were studied. Conventional RT, 3D-CRT, and step-and-shoot IMRT plans were prepared using the same 2-field arrangement. The effect of reducing the number of segments in the IMRT beams was investigated. 3D-CRT and IMRT reduced the brain and ipsilateral parotid gland doses compared with the conventional plans. IMRT reduced doses to both optic nerves; for the contralateral optic nerve, 15-segment IMRT plans delivered an average maximal dose of 56.4 Gy (range 53.9–59.3) compared with 65.7 Gy (range 65.3–65.9) and 64.2 Gy (range 61.4–65.6) for conventional RT and 3D-CRT, respectively. IMRT also gave improved PTV homogeneity and improved coverage, with an average of 8.5% (range 7.0–11.7%) of the volume receiving

Oral Resveratrol Reduces Neuronal Damage in a Model of Multiple Sclerosis

Background: Neuronal loss in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), correlates with permanent neurological dysfunction. Current MS therapies have limited the ability to prevent neuronal damage. Methods: We examined whether oral therapy with SRT501, a pharmaceutical grade formulation of resveratrol, reduces neuronal loss during relapsing-remitting EAE. Resveratrol activates SIRT1, an NAD-dependent deacetylase that promotes mitochondrial function. Results: Oral SRT501 prevented neuronal loss during optic neuritis, an inflammatory optic nerve lesion in MS and EAE. SRT501 also suppressed neurological dysfunction during EAE remission, and spinal cords from SRT501-treated mice had significantly higher axonal density than vehicle-treated mice. Similar neuroprotection was mediated by SRT1720, another SIRT1-activating compound; and sirtinol, an SIRT1 inhibitor, attenuated SRT501 neuroprotective effects. SIRT1 activators did not prevent inflammation. Conclusions: These studies demonstrate that SRT501 attenuates neuronal damage and neurological dysfunction in EAE by a mechanism involving SIRT1 activation. SIRT1 activators are a potential oral therapy in MS. © 2010 by North American Neuro-Ophthalmology Society.

Anatomy and physiology of the human eye: effects of mucopolysaccharidoses disease on structure and function - a review

P>The current paper provides an overview of current knowledge on the structure and function of the eye. It describes in depth the different parts of the eye that are involved in the ocular manifestations seen in the mucopolysaccharidoses (MPS). The MPS are a group of rare inheritable lysosomal storage disorders characterized by the accumulation of glycosaminoglycans (GAGs) in cells and tissues all over the body, leading to widespread tissue and organ dysfunction. GAGs also tend to accumulate in several tissues of the eye, leading to various ocular manifestations affecting both the anterior (cornea, conjunctiva) and the posterior parts (retina, sclera, optic nerve) of the eye.

Environmental tobacco smoke exposure and eye disease

Aim: To undertake a systematic review of the literature on the effect of environmental tobacco smoke (ETS) and eye disease. Methods: Medline (1950-January Week 2 2007), EMBASE (1980 to 2007 Week 07), SCOPUS and Science Direct were searched on ETS exposure and eye disease using various combinations of the following terms: passive smoking, environmental tobacco smoke, sidestream smoke, involuntary smoking, secondhand smoke; with eye, conjunctiva, sclera, episclera, cornea, lens, iris, retina, choroid, uvea, optic nerve, uveitis, iritis, blindness, visual loss, cataract, thyroid eye disease, conjunctivitis, age-related macular degeneration, dry eye, tears. The above terms were also used to search abstracts published on The Association for Research in Vision and Ophthalmology Annual Meeting abstracts, from 1995 to 2006, and the grey literature, including PhD and MSc theses/dissertations. A search was further conducted specifically on eye diseases where active smoking has been proposed to be a risk factor, including age-related macular degeneration, Graves ophthalmology, glaucoma, uveitis, refractive errors, strabismus, tobacco-alcohol amblyopia, non-arteritic ischaemic optic neuropathy, Leber optic neuropathy and diabetic retinopathy. Given the scarce number of studies found through the above search, all articles found on ETS and eye disease were included in this review. Results: Seven studies evaluated the possible relationship between ETS and an eye disease. These studies referred to refractive errors in children (n = 2), cataract (n = 1), age-related macular degeneration (n = 3) and Grave ophthalmopathy (n = 1). The data available were insufficient to establish conclusive relationships between ETS and these eye diseases. Conclusion: Very scarce data exist in the literature on the effect of ETS on diseases of the eye. It seems appropriate that ETS should be included in future studies addressing the effect of smoking on eye disease.

Surveillance for ocular hypertension: An evidence synthesis and economic evaluation

OBJECTIVES: To determine effective and efficient monitoring criteria for ocular hypertension [raised intraocular pressure (IOP)] through (i) identification and validation of glaucoma risk prediction models; and (ii) development of models to determine optimal surveillance pathways.

DESIGN: A discrete event simulation economic modelling evaluation. Data from systematic reviews of risk prediction models and agreement between tonometers, secondary analyses of existing datasets (to validate identified risk models and determine optimal monitoring criteria) and public preferences were used to structure and populate the economic model.

SETTING: Primary and secondary care.

PARTICIPANTS: Adults with ocular hypertension (IOP > 21 mmHg) and the public (surveillance preferences).

INTERVENTIONS: We compared five pathways: two based on National Institute for Health and Clinical Excellence (NICE) guidelines with monitoring interval and treatment depending on initial risk stratification, 'NICE intensive' (4-monthly to annual monitoring) and 'NICE conservative' (6-monthly to biennial monitoring); two pathways, differing in location (hospital and community), with monitoring biennially and treatment initiated for a ≥ 6% 5-year glaucoma risk; and a 'treat all' pathway involving treatment with a prostaglandin analogue if IOP > 21 mmHg and IOP measured annually in the community.

MAIN OUTCOME MEASURES: Glaucoma cases detected; tonometer agreement; public preferences; costs; willingness to pay and quality-adjusted life-years (QALYs).

RESULTS: The best available glaucoma risk prediction model estimated the 5-year risk based on age and ocular predictors (IOP, central corneal thickness, optic nerve damage and index of visual field status). Taking the average of two IOP readings, by tonometry, true change was detected at two years. Sizeable measurement variability was noted between tonometers. There was a general public preference for monitoring; good communication and understanding of the process predicted service value. 'Treat all' was the least costly and 'NICE intensive' the most costly pathway. Biennial monitoring reduced the number of cases of glaucoma conversion compared with a 'treat all' pathway and provided more QALYs, but the incremental cost-effectiveness ratio (ICER) was considerably more than £30,000. The 'NICE intensive' pathway also avoided glaucoma conversion, but NICE-based pathways were either dominated (more costly and less effective) by biennial hospital monitoring or had a ICERs > £30,000. Results were not sensitive to the risk threshold for initiating surveillance but were sensitive to the risk threshold for initiating treatment, NHS costs and treatment adherence.

LIMITATIONS: Optimal monitoring intervals were based on IOP data. There were insufficient data to determine the optimal frequency of measurement of the visual field or optic nerve head for identification of glaucoma. The economic modelling took a 20-year time horizon which may be insufficient to capture long-term benefits. Sensitivity analyses may not fully capture the uncertainty surrounding parameter estimates.

CONCLUSIONS: For confirmed ocular hypertension, findings suggest that there is no clear benefit from intensive monitoring. Consideration of the patient experience is important. A cohort study is recommended to provide data to refine the glaucoma risk prediction model, determine the optimum type and frequency of serial glaucoma tests and estimate costs and patient preferences for monitoring and treatment.

FUNDING: The National Institute for Health Research Health Technology Assessment Programme.

Developing the specifications of an open angle glaucoma screening intervention in the United Kingdom: a Delphi approach.

Abstract
BACKGROUND:
Glaucoma is a leading cause of blindness. Early detection is advocated but there is insufficient evidence from randomized controlled trials (RCTs) to inform health policy on population screening. Primarily, there is no agreed screening intervention. For a screening programme, agreement is required on the screening tests to be used, either individually or in combination, the person to deliver the test and the location where testing should take place. This study aimed to use ophthalmologists (who were experienced glaucoma subspecialists), optometrists, ophthalmic nurses and patients to develop a reduced set of potential screening tests and testing arrangements that could then be explored in depth in a further study of their feasibility for evaluation in a glaucoma screening RCT.
METHODS:
A two-round Delphi survey involving 38 participants was conducted. Materials were developed from a prior evidence synthesis. For round one, after some initial priming questions in four domains, specialists were asked to nominate three screening interventions, the intervention being a combination of the four domains; target population, (age and higher risk groups), site, screening test and test operator (provider). More than 250 screening interventions were identified. For round two, responses were condensed into 72 interventions and each was rated by participants on a 0-10 scale in terms of feasibility.
RESULTS:
Using a cut-off of a median rating of feasibility of =5.5 as evidence of agreement of intervention feasibility, six interventions were identified from round 2. These were initiating screening at age 50, with a combination of two or three screening tests (varying combinations of tonometry/measures of visual function/optic nerve damage) organized in a community setting with an ophthalmic trained technical assistant delivering the tests. An alternative intervention was a 'glaucoma risk score' ascertained by questionnaire. The advisory panel recommended that further exploration of the feasibility of screening higher risk populations and detailed specification of the screening tests was required.
CONCLUSIONS:
With systematic use of expert opinions, a shortlist of potential screening interventions was identified. Views of users, service providers and cost-effectiveness modeling are now required to identify a feasible intervention to evaluate in a future glaucoma screening trial.

What is the best method for diagnosing glaucoma?

Glaucoma is characterized by a typical appearance of the optic disc and peripheral visual field loss. However, diagnosis may be challenging even for an experienced clinician due to wide variability among normal and glaucomatous eyes. Standard automated perimetry is routinely used to establish the diagnosis of glaucoma. However, there is evidence that substantial retinal ganglion cell damage may occur in glaucoma before visual field defects are seen. The introduction of newer imaging devices such as confocal scanning laser ophthalmoscopy, scanning laser polarimetry and optical coherence tomography for measuring structural changes in the optic nerve head and retinal nerve fiber layer seems promising for early detection of glaucoma. New functional tests may also help in the diagnosis. However, there is no evidence that a single measurement is superior to the others and a combination of tests may be needed for detecting early damage in glaucoma. © 2010 Expert Reviews Ltd.

Methods to objectify reversibility of glaucomatous cupping

Lowering intraocular pressure in adults with glaucoma may be associated with an improvement in appearance of the optic nerve head. The stage of disease, the amount of intraocular pressure reduction, and the age of the patient probably influence the occurrence of this event. The clinical relevance of 'reversal' has not been established with certainty. The reversibility of glaucomatous cupping can be detected by subjective and qualitative means (examination of the patient or of fundus photographs) or by quantitative techniques such as photogrammetry, computerized image analysis, and scanning laser tomography. Clinical and experimental studies are providing new information about the behavior of the optic nerve head tissues in response to changes in intraocular pressure.

Cannabinoids and glaucoma - A review

Glaucoma is one of the leading causes of blindness in the world. A wide range of therapeutic possibilities to control the disease and prevent glaucomatous optic nerve damage with subsequent loss of vision already exist. In a relatively high proportion of patients, medical and/or surgical therapies are contraindicated or become non-effective. The purpose of this article is to provide an overview on the latest achievements in the research of potential use of cannabinoids in glaucoma. Methods: The literature on recent basic science research on cannabinoids and a range of research studies using cannabinoids under different preparations and ways of application was reviewed. Conclusions: Cannabinoids effectively lower the intraocular pressure. Newer research findings allow a better understanding of the different possible mechanisms of action of cannabinoids on IOP. Future progress in different research fields concerning possible clinical applications of cannabinoids may offer better preparations with less or possibly no undesired side effects.

Incidence of glaucoma in patients with uveitis

Purpose: To evaluate the incidence of glaucoma and elevation of intraocular pressure (IOP) in patients with inflammatory eye disease. Methods: Retrospective review of medical records of 391 consecutive patients with uveitis attending a uveitis clinic of an academic Department of Ophthalmology from January 1999 to August 2002. Demographic, ocular and systemic variables were recorded. The diagnosis and treatment of uveitis were recorded. Uveitis was classified according to standard anatomic, etiological and clinical criteria. "Glaucoma" was defined as elevated IOP (>21 mm Hg) or glaucomatous optic nerve damage requiring medical and/or surgical anti-glaucoma treatment. Kaplan-Maier analysis and log-rank tests were used to evaluate and compare the incidence of glaucoma. Results: The incidence of glaucoma as defined above at 3 and 12 months after acute uveitis was 7.6%. In patients with chronic uveitis (n = 337), the incidence of glaucoma at 1 and 5 years was 6.5% and 11.1%, respectively. There was no statistically significant difference in the incidence of glaucoma between different types of uveitis, idiopathic versus non-idiopathic, and among anterior, intermediate, posterior and panuveitis. Visual loss occurred more frequently in patients with glaucoma than in patients without glaucoma. Conclusion: In patients with chronic inflammatory eye disease, the presence of glaucoma was associated with an increasing risk of visual loss. The incidence of glaucoma increased with time and was similar among the different types of uveitis.

Clinical and experimental links between diabetes and glaucoma

Glaucoma is a leading cause of blindness. It is a multifactorial condition, the risk factors for which are increasingly well defined from large-scale epidemiological studies. One risk factor that remains controversial is the presence of diabetes. It has been proposed that diabetic eyes are at greater risk of injury from external stressors, such as elevated intraocular pressure. Alternatively, diabetes may cause ganglion cell loss, which becomes additive to a glaucomatous ganglion cell injury. Several clinical trials have considered whether a link exists between diabetes and glaucoma. In this review, we outline these studies and consider the causes for their lack of concordant findings. We also review the biochemical and cellular similarities between the two conditions. Moreover, we review the available literature that attempts to answer the question of whether the presence of diabetes increases the risk of developing glaucoma. At present, laboratory studies provide robust evidence for an association between diabetes and glaucoma.